AMG-517 - TRP Channel Antagonist - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAMG 517Cat. No.: HY-10634CAS No.: 659730-32-2分式: CHFNOS分量: 430.4作靶点: TRP Channel作通路: Membrane Transporter/Ion Channel; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 12.9

2、1 mg/mL (30.00 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.3234 mL 11.6171 mL 23.2342 mL5 mM 0.4647 mL 2.3234 mL 4.6468 mL10 mM 0.2323 mL 1.1617 mL 2.3234 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，

3、建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.81 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.81 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您边的抑制剂师w

4、ww.MedChemE物活性 AMG 517有效的草素受体-1 (TRPV1) 拮抗剂，IC50值为0.5 nM。IC50 & Target IC50: 0.5 nM (TRPV1) 1体外研究 AMG 517 retains potency in the capsaicin- and acid-mediated assays with IC50 values of 0.9 and 0.5 nM 1.AMG 517 inhibits capsaicin, pH 5, and heat-induced45Ca2+ uptake into cells expressing TRPV1 with I

5、C50values of 1 to 2 nM. AMG 517 blocks capsaicin-, proton-, and heat-induced inward currents in TRPV1-expressing cells similarly. AMG 517 inhibits native TRPV1 activation by capsaicin in rat dorsal root ganglionneurons with an IC50 value of 0.68 0.2 nM. AMG 517 is a competitive antagonist of both ra

6、t and humanTRPV1 with dissociation constant (Kb) values of 4.2 and 6.2 nM, respectively 2.体内研究 AMG 517 is shown to be effective in a rodent “on-target” biochemical challenge model (capsaicin-inducedflinch, ED50=0.33 mg/kg p.o.) and is antihyperalgesic in a model of inflammatory pain (CFA-induced the

7、rmalhyperalgesia, MED=0.83 mg/kg, p.o.) 1.The minimally effective dose is 0.3 mg/kg for AMG 517 and thecorresponding plasma concentration is 90 ng/mL. Oral administration of AMG 517 reverses establishedthermal hyperalgesia in a dose-dependent manner at 21 h after CFA injection. AMG 517 causes transi

8、enthyperthermia in rodents, dogs, and monkeys. AMG 517 induces hyperthermia in a steep dose-dependentmanner, with 0.3, 1, and 3 mg/kg associated with 0.5, 0.6, and 1.6C increases in body temperature,respectively. Body temperatures of rats treated with all doses of AMG 517 return to baseline within 1

9、0 to 20 h2.PROTOCOLAnimal Rats: After multiple days of full habituation to the testing equipment and paradigm, CFA-induced thermalAdministration 2 hyperalgesia is evaluated by measuring paw withdrawal latencies in male Sprague-Dawley rats. Twenty-onehours after CFA injection (50 L of 0.1%), animals

10、are dosed (p.o.) with AMG 517 or AMG8163 at a doserange of 0.001 to 30 mg/kg in a volume of 5 mL/kg. Two hours after drug dosing (23 h after CFA injection),paw withdrawal latencies are measured using modified Hargreaves hot boxes by investigators fully blinded totreatment conditions 2.MCE has not in

11、dependently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 EMBO Rep. 2016 Oct;17(10):1422-1430. Biophys J. 2017 Jan 10;112(1):87-98.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Doherty EM, et al. Novel vanilloid receptor-1 antagonists: 2. St

12、ructure-activity relationships of 4-oxopyrimidines leading to the selectionof a clinical candidate. J Med Chem. 2007 Jul 26;50(15):3515-27.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE2. Gavva NR, et al. Repeated administration of vanilloid receptor TRPV1 antagonists attenuates hyperthermia elicited by TRPV1 blockade.J Pharmacol Exp Ther. 2007 Oct;323(1):128-37.McePdfHeightCautio